肺癌细胞免疫组分子表达特征及其对早期免疫应答的塑型作用与机制

上皮细胞受刺激和坏死时，表达的免疫效应分子（上皮免疫组）对早期应答的活化与方向具有指导作用。肺癌细胞源于肺上皮细胞，而癌变情况下肺癌细胞中免疫分子的表达（癌细胞免疫组）因表观遗传调控可能发生异常，在应答早期未能有效触发免疫活化、对I型免疫应答未能作出正确指导或对免疫应答造成抑制，从而造成肺癌免疫应答失衡和肿瘤逃逸。.本项目旨在我们对部分上皮性细胞因子的功能、表达与肿瘤发生初步研究的基础上：系统阐明肺癌细胞免疫组表达异常及其与应答早期免疫应答失衡、肿瘤特异性免疫应答水平低下等之间的关系；对表达水平与肿瘤免疫应答呈显著负相关的肺癌细胞免疫组分子，在本培育项目中选择2-3个，解析其异常沉默或上调的表观调控机制；进一步探讨分别恢复这2-3个分子在肺癌细胞的表达特性后，对早期免疫应答格局的改观；从而揭示肺癌细胞免疫组表达特征及其对早期免疫应答的塑型作用与机制，为肺癌免疫干预奠定理论基础。

The epithelial cells, when being stimulated or undergoing necrocytosis, can exert an important role in activating and modulating the innate and adaptive immune responses by expressing cytokines, chemokines and surface molecules (Epimmunome). Since being derived from lung epithelial cells, the lung cancer cells can produce a series of such immune molecules during tumorigenesis (Cancer cell immunome), which is generally characterized by inflammation and necrosis. However, the expression patterns of these molecules in lung cancer cells during tumorigenesis may be skewed, which are different from that in normal lung epithelial cells with stimulation or nerocytosis, resulting in immune regression and tumor cell escape..On the basis of our studying of the regulation and function of several molecules from epimmunome on tumorigensis, this project aims to explore the function and mechanism of the expression patterns of immunome of lung cancer cells on shaping early immune responses by developing some plans as follows. 1. To systematically analyze the correlation of the expression patterns of cancer cell immunome with the polarization of immune subsesets, the expression characteristics of immune molecules and the levels of tumor-specific immune responses. 2. In this project, to reveal the mechanism of epigenetic regulation of 2∼3 molecules, the silence or up-expression of which is negatively correlated with anti-tumor immune responses respectively. 3. To identify the early anti-lung cancer immune response can be improved by recovering or down-regulating the target molecules.